Periorbital Hyperchromia Review Article Hiperpigmentação Periorbital

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Periorbital hyperchromia Review Article Hiperpigmentação periorbital

Authors: ABSTRACT Daniela Moraes Souza1 Cristiane Ludtke1 Peri orbital hyperchromia (dark eye circles) is a recurrent complaint in dermatologic con- Emanuelle Rios de Moraes Souza2 sultations, as it interferes with patients’ self esteem. The eyes are central in the communi- Karina Melchiades Pinheiro Scandura2 Magda Blessmann Weber3 cation process, and dark eye circles are very noticeable and make the face look tired; thus they have a considerable impact on patients’ quality of life. Although many treatment

options are available, publications on periorbital hyperpigmentation are scarc e, and the 1 Dermatology specialist candidate, vast majority lack a sound scientific basis to prove their efficacy and duration. This article Universidade Federal de Ciências da Saúde analyzes the palpebral regi on’s anatomy and periorbital hyperchromia’s epidemiology, de Porto Alegre (UFCSPA) – Porto Alegre (RS), Brazil. etiopathogeny, and treatments recommended in the literature. 2 Intern, Dermatology Department, Keywords: hyperpigmentation; eyelids; skin pigmentation; products for eye areas. Univer sidade Federal de Ciências da Saúde de Porto Alegre 3 Assistant Professor, Universidade Federal de Ciências da Saúde de Porto Alegre RESU MO A hipercromia cutânea periorbital ou "olheira" é queixa comum nos consultórios de dermatologia por interferir na autoestima dos pacientes. Os olhos são o centro das atenções na comunicação, e a "olheira" dificilmente passa despercebida, proporcionando à fa ce aspecto de cansaço, causando impor- tante impacto na qualidade de vida. Há poucas publicações na literatura sobre hiperpigmentação periorbital e, embora as opções de tratamento sejam muito vastas, a maioria carece de embasamento cien- tífico que comprove sua eficácia e duração. Este artigo aborda a anatomia da região palpebral, a epi- demiologia, a etiopatogenia e os tratamentos propostos na literatura para a hipercromia periorbital. Correspondence: Pa lavras-chave: hiperpigmentação; pálpebras; pigmentação da pele; produtos para áreas dos olhos. Universidade Federal de Ciências da Saúde de Porto Alegre Centro de Saúde Santa Marta Serviço de Dermatologia Rua Capitão Montanha, 27 / 3ºandar, sala 324 90010 040 – Porto Alegre – RS, Brazil E-mail: [email protected]

INTRODUCTION Although periorbital hyperpigmentation (also called peri- palpebral hyperpigmentation, dark eyelids, dark eye circles, dark circles, or simply under-eye circles) is a mere color difference between the palpebral skin and the remaining facial skin, it makes people look tired or older, which negatively affects their quality of life.1,-4 It has a higher prevalence in individuals with darker skin, hair and eyes, and affects age groups and genders equally. Nevertheless, there are a higher number of complaints from Received on: 17/07/2011 Approved on: 08/09/2011 women, especially senior women. There are few studies about the etiology of this condition, however dark eye circles with a This study was carried out at the Universidade Federal de Ciências da Saúde de Porto Alegre vascular component are known to present a dominant autoso- (UFCSPA) – Porto Alegre (RS), Brazil mal family inheritance pattern.2,3 Periorbital hyperpigmentation seems to have multifactori- Conflicts of interests: none Financial support: none al causes that involve intrinsic factors (determined by the individual’s genetics), and extrinsic factors (sun exposure, smoking,

Surg Cosmet Dermatol 2011;3(3):233-9. 234 Souza DM, Ludtke C, Souza ERM, Scandura KMP, Weber MB alcoholism and sleep deprivation, for instance). However, the upper eyelid, 14 which is caused by a decrease in the upper eye- presence of melanic pigment and hemosiderotic pigment in the lid lifter muscle’s aponeurosis action.15 The skin becomes more affected sites is a distinctive feature in its etiopathogeny.2-4 flaccid, less elastic and has a greater propensity to wrinkle 16. Melanic hyperpigmentation is more frequent in brunet The orbicular and tarsal muscles, the orbital septum and the adults, as a consequence of excessive and cumulative exposure to conjunctival mucous membrane also go through transforma- the sun, which increases the production of melanin, reduces the tions in the elderly. In addition, gravity and facial expressions skin’s thickness and increases the dilatation of blood vessels.2,4,5 influence the mechanical deformation of those structures. 17 Intense vascularization is mainly found in people belong- A cohort study with 320 patients (aged 10-89) evaluated ing to certain ethnic groups such as Arabs, Turks, Hindus, inhab- participants’ eyelids frontally and laterally and found that there is itants of the Iberian Peninsula and their respective descendants. a correlation between a decrease in the palpebral fissure and an In these ethnicities, its manifestation tends to take place earlier, increase in the age of patients. 19 often during childhood. In those individuals there is no change in the color of the skin; the eyelid appears darkened because the PALPEBRAL REGION’S SKIN AND SUBCUTANEOUS TISSUE dilated vessels are visible due to the transparency of the skin. 2 In Palpebral skin is the thinnest in the human body (< 1 mm). those cases, therefore, the problem is often aggravated when the Its epidermis is constituted of stratified epithelium, which is lower eyelid’s vessels are more dilated (e.g., from fatigue, insom- very thin (0.4 mm) compared to that of the palmoplantar region nia, oral breathing, crying), causing dermal blood extravasation. (the thickness of which is approximately 1.6 mm).13 The liberation of ferric ions takes place locally, entailing the for- The nasal portion of the palpebral skin has thinner hair and mation of free radicals that stimulate the melanocytes, which more sebaceous glands (i.e., it is softer and oilier) than its tem- generates melanic pigmentation. 2, 4-6 poral portion. The transition between the eyelids’ thin skin and Other causes noted as being responsible for the appearance the remaining facial skin is clinically observable.13 of dark eye circles are post-inflammatory hyperpigmentation The palpebral dermis is composed of loose conjunctive secondary to atopic and contact dermatitis, sleep deprivation, tissue, and is extremely thin in that region. It is absent in the oral breathing, alcoholism, smoking, use of certain medications pre-tarsal skin, in the medial and lateral ligaments of the eyelid, (contraceptives, chemotherapy, antipsychotic and some types of where the skin adheres to the underlying fibrous tissue. The eye drops), the presence of palpebral sagging (due to aging) and thinness of the skin, combined with the lack of fatty tissue, gives of disorders that develop with hydric retention and palpebral that region its characteristic translucency. As a result, the accu- edema (thyroid disorders, nephropathies, cardiopathies and mulation of melanin and/or vessel dilatation in that region can pneumopathies) – all of which worsen the unattractive appear- be easily seen, through transparency, as bilateral homogeneous ance of dark eye circles.2-4,7 hyperpigmentation.2,4,5,13 Various treatments have been proposed for periorbital hyperchromia, however there are few studies on their long-term PALPEBRAL REGION’S VENOUS AND LYMPH efficacy. The main types of treatment are: topical application of VASCULARIZATION depigmenting products, chemical peelings, dermabrasion, The eyelids’ arterial irrigation comes through many vessels: cryosurgery, fillings with hyaluronic acid, intense pulsed light, the supratrochlear, supraorbital, lachrymal and dorsum of the CO2, argon, ruby and excimer lasers. 2-4, 6, 8-12 nose arteries (all originating in the facial artery); the angular artery (originating in the facial artery); the transverse artery PALPEBRAL ANATOMY (originating in the facial artery); the transverse facial artery The eyelids are tegumentary pleats that participate in facial (originating in the superficial temporal artery) and the branch- expression and aesthetics, however their main function is to pro- es of the superficial temporal artery itself 20 (Figure 1). tect the eyeballs through sensorial filtration actions carried out Venous drainage (following an external pattern) takes place by the palpebral cilia, and the Meibomian and lachrymal glands’ through the veins associated with these arteries and (following secretions. In this manner, the cornea remains hydrated and the an internal pattern) penetrates the orbit through connections closing movements of the eyes function as a barrier to external with ophthalmic veins 20 (Figure 2). traumas and prevent the cornea from drying out.13-17 Lymphatic drainage takes place mainly through the parotid The upper eyelid reaches upwards to the eyebrow, which lymph nodes; some of the drainage from the medial angle of the separates it from the forehead. The lower eyelid extends down- eye to the lymph vessels is associated with the angular and facial wards up to the lower border of the orbit, and is delimited by arteries, towards the submandibular lymph nodes.20 the genian region.15 The palpebral fissure, which measures 9-10 mm in adults, COLOR OF THE SKIN IN THE PALPEBRAL REGION is determined by the interaction of the muscles that open and The palpebral skin’s color results from the combination of close the eyelids. To open the eyelid, the palpebral elevator mus- several factors, some of genetic-racial origin (such as the amount cle is assisted by two other accessory muscles (Muller’s and of melanin pigment), others of individual or regional and even frontalis muscles).18 The aging process decreases the palpebral fis- gender l origins, such as the thickness of the several components sure’s vertical opening, due to the progressive lowering of the and the blood volume in their vessels.2,4,5,21

Surg Cosmet Dermatol 2011;3(3):233-9. Periorbital hyperchromia 235

Supraorbital artery

Supratrochlear artery Superficial temporal artery’s frontal branch Dorsal artery of the nose

Superior lateral palpebral artery Superior medial palpebral arteries

Inferior lateral palpebral artery Angular artery

Inferior medial Zygomaticofacial artery palpebral arteries Superior and inferior palpe- Transverse facial artery bral arches

Infraorbital artery Facial artery Figure 1 - Eyelids’ arterial irrigation

DARK EYE CIRCLES’ ETIOPATHOGENY There are two types of dark eye circles: those of predomi- milar analogous prostaglandins for the treatment of glaucoma nantly vascular etiology and those of predominantly melanic eti- causes, in addition to palpebral hyperpigmentation, the ology. The majority, however, have mixed origins and are caused reabsorption of orbital fat.3,26 by the combination of the pigments melanin and hemosiderin.2-4 A deficiency in vitamin K, vital in the blood coagulation Dark circles with a predominantly vascular etiology pre sent process, can cause small hemorrhages and cause dark circles.2,3,25 a pattern of dominant autosomal family inheritance. 2-4 They usually appear earlier, during childhood or adolescence, and are EPIDEMIOLOGY more common in Arab, Turkish, Hindu and Iberian ethnic No epidemiological studies carried out in patients with groups.2 Diagnosing the type of dark eye circles is carried out periorbital hyperpigmentation were found in the researched li- by tractioning the lower eyelid in order to better visualize the terature. transparency of the vessels under the skin 2 (Figure 3). It is believed that dark eye circles and palpebral affections Dark eye circles of predominantly melanic etiology occur are more frequent in women and in individuals with darker skin, more frequently in patients with higher phototypes (Figure 4), hair and eyes,regardless of their etiology. It affects all age groups, but can affect patients with lower phototypes – usually older however it is more evident in older people.2-4 After menopause, patients who have had excessive and cumulative sun expo- cutaneous collagen synthesis decreases 2.1% per year, and as the sure.2,22-24 hypodermis becomes thinner, the skin’s aesthetic condition The physiological cutaneous aging process that leads to worsens. The aging process also causes structural changes in the palpebral flaccidity and sagging worsens the dark circles’ appear- skin due to gravity and physiological alterations in the skin, ance. In addition, excessive exposure to the sun, which causes an which can be more intense when combined with actinic da - increase in pigmentation, a decrease in the thickness of the skin mage. When acting in an area that is low in collagen or subcuta- and local vasodilatation, can be a significant etiologic factor for neous tissue, or in areas with little muscular sustentation, gravity dark eye circles.2,7,14-16,25 causes the skin to move downwards, becoming stretched and Due to the vasoconstricting effects of nicotine, smoking thinner, making the palpebral vessels more visible. 2,6,14,16,25 causes a pale appearance of the skin in general, increasing the Ohshima and colleagues studied palpebral skin and noticed contrast with under-eye circles; alcoholism and sleep depriva- that it is significantly less dense in patients with dark eye circles, tion cause vasodilatation and an increase in palpebral blood which allows a clearer visualization of vessels and pigmentation flow; oral breathing causes edema in the nasal and paranasal due to the transparency of this area.7 mucous membrane, obstructing the palpebral veins’ drainage and leading to blood stasis and dark circles.2,25 TOPICAL TREATMENTS The use of hormonal replacement therapy and contracep- Periorbital hyperpigmentation is a common complaint in tives, and menstruation and pregnancy worsen under-eye circles dermatology practices. However, it is rarely studied. Since it due to the hormonal stimulus of melanin production.2,3,22,25 does not have a clearly defined etiopathogeny, there is no con- The use of vasodilating drugs and eye drops based on si- sensus regarding its treatment.

Surg Cosmet Dermatol 2011;3(3):233-9. 236 Souza DM, Ludtke C, Souza ERM, Scandura KMP, Weber MB

Supratrochlear vein Nasofrontal vein Supraorbital vein

Angular vein Superior ophthalmic vein

Cavernous sinus

Vorticose veins

Inferior ophthalmic vein Facial vein

Pterygoid plexus

Maxillary vein Figure 2 - Eyelids’ venous Retromandibular vein Deep facial vein drainage

Most topical treatments consist of the application of de- significantly smaller on the side treated with sodium ascorbate pigmenting products (vitamins C, E and K1; azelaic, phytic and compared to the side treated with the vehicle. The dermal kojic acids; arbutin; biosome C; magnesium ascorbyl phosphate; thickness was greater on the side treated with sodium ascorbate thioglycolic acid; hydroquinone; haloxyl). Nevertheless, there compared to the other side, but the difference was not statisti- are few studies analyzing or comparing the efficacy of those cally significant. No significant differences were observed medications or correlating the results with patients’ epidemio- between the sides treated with ascorbic acid glucoside and those logical characteristics.2-4,25 treated with the vehicle regarding the erythema index, An open, monocentric, non-paired clinical and non-ran- echogenicity or dermal thickness. The authors concluded that domized pilot study was recently published that demonstrated sodium ascorbate can improve dark eye circles by increasing the the efficacy and safety of treating infraorbicular pigmentation lower eyelids’ thickness and reducing the dark staining caused by with 10% acid thioglycolic gel peeling. The study included 10 the congestion of blood circulation.29 volunteers, aged 24-50, who underwent five sessions of peeling A study combining 2% phytonadione, 0.1% retinol, 0.1% with 10% acid thioglycolic gel at 15-day intervals. The average vitamin C and 0.1% vitamin E in a gel, applied twice a day for clinical satisfaction rated by patients was 7.8; that of the applica- eight weeks in 57 patients’ lower eyelids, demonstrated that 27 tor physician was 7.6; and that of the evaluator blunt physician (47%) presented reduced pigmentation; the procedure was con- was 6.8, with no statistically significant difference between them sidered by the authors to be very or moderately effective in the (p = 0.065).3 Thioglycolic acid, a depigmenter with an unpleas- reduction of dark eye circles.6 ant scent, is suitable for hyperchromias with a predominantly Hydroquinone is a topical depigmenting agent that acts vascular component, due to its capacity to absorb the hemoglo- immediately by inhibiting the tyrosinase’s activity. Secondarily, bin’s iron oxide, alleviating the dark eye circles.3,27 and more slowly, it induces structural modifications in the Ascorbic acid is a depigmenting agent that is less chemical- membranes of the organelles of the melanocytes, accelerating ly stable in topical formulations. In addition to its whitening the degradation of the melanosomes.7,14 A combined study con- effect, it can also increase collagen synthesis, improving the skin’s ducted with 18 patients who used 5% hydroquinone gel and thickness, and in turn attenuate dark eye circles. Preference 0.1% retinoic acid for six weeks, followed by the application of should be given to magnesium ascorbyl phosphate, a vitamin C q-switched Ruby laser with the purpose of reducing epidermal derivative that is more stable and acts by inhibiting melanogen- and dermal pigmentation, respectively, showed excellent results esis. 28 Ohshima and others conducted a clinical study to evalu- that were confirmed by the patients’ satisfaction level (consid- ate vitamin C’s efficacy in treating dark eye circles. Volunteers (n ered excellent by 83.3%) and by the skin biopsies carried out = 14) with lower eyelid hyperpigmentation were evaluated for before and after treatment (which demonstrated a decrease in six months, using a solution containing 10% sodium ascorbate dermal pigmentation in all patients).14 There are several cosme- on one side of the face and ascorbic acid glucoside on the other. ceuticals containing hydroquinone in the market, however none The melanin and erythema indices, thickness and the inferior of them was specifically formulated for the treatment of the eye papillae dermis’ echogenicity were evaluated bilaterally during area. The safety and efficacy of using those creams to treat the course of the study. The change in the erythema index was hyperpigmentation in conditions other than melasma have not

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LASER AND INTENSE PULSED LIGHT TREATMENTS The use of intense pulsed light is recommended in the treatment of vascular dark eye circles due to its capacity to stim- Figure 3 - Periorbital hyper- ulate collagen synthesis and improve the skin’s texture and color pigmentation of by selectively stimulating the temperature at the desired depth, 12 vascular pattern. without heating up the skin’s surface. Visualization of the Intense pulsed light is more suitable for treating poikilo- vascularization derma of Civatte, rosacea vascular lesions and solar melanoses, under the skin but can present good results in infraorbital hyperpigmentation when tractioning after one to three sessions.12 the inferior eyelid West and Alster observed the whitening of the infraorbital skin after nine weeks of treatment with intense pulsed light, however the melanin spectrometry did not correlate with the results. Cymbalista described the clinical whitening of the lower eyelid’s skin, and the maintenance of the results, without recur- rence, after one year of treatment with intense pulsed light.8 Manuskiatti and others demonstrated that the combination of several laser types (CO2, Q-switched Alexandrite, Er: YAG Figure 4 - and pulsed dye lasers ) in a single session presented 75-100% Predominantly positive results, with no reported complications.9 melanic periorbital The combination of epidermal ablation with the CO2 and hyperpigmentation in phototype VI Q-switched Alexandrite lasers presents better results than the patient use of the same lasers individually to treat dark eye circles. If the pigment is mainly originating in the epidermis, CO2 removes it more efficiently, reaching a depth closer to the dermis, where yet been studied.30-32 Q-switched Alexandrite complements the therapy. The effects Haloxyl is an anti-dark eye circles active substance that was begin to appear six to eight weeks after the treatment. 9 The iso- shown to be effective in a study carried out in 22 patients who lated use of CO2 laser can also demonstrate good results, as in a applied a gel containing 2% haloxidyl around one eye for 56 study by West and Alster, carried out in a group of 12 patients, days. Participants were later evaluated by analyzing images using with a 50% improvement after nine weeks of treatment.10 specialized software that gauged the shade of the dark circles. The 694 nm q-switched Rubi laser has also demonstrated Haloxidyl is composed of chrysin, N-hydroxysuccinimide and good results in the treatment of periorbital hyperpigmentation; matrikines – peptides liberated by extracellular matrix macro- Lowe and others 36 had 88.9% satisfactory responses in 17 molecules’ proteolysis. That medication’s components seem to patients and Watanabe and colleagues 37 had excellent results in act synergically in the reduction of dark eye circles. Matrikines two patients and good results in two of their other five patients. stimulate the synthesis of the extracellular matrix’s components, Erbium laser can also be a good option for dark eye circles. reinforcing the palpebral tonus, while the chrysin and the N- With a 2,940 nm wavelength and water as its chromophore, it hydroxysuccinimide act as bilirubin and iron chelators, respec- is recommended for some conditions in which there are con- tively, reducing local pigmentation.33 straints for the use of CO2 laser. Erbium-YAG laser has weaker Phytomenadione (phytokine) is synthetic vitamin K, which thermal and greater ablative effects; it can eliminate pigment performs the same functions as natural vitamin K. It participates without stimulating the formation of new pigment. in the coagulation factors II, VII, IX and X synthesis, and acts as Nonetheless, as its effects are superficial, deeper ablations (at the an essential cofactor in the post-transductional carboxylation of papillary dermis depth or deeper) cause bleeding. Whitening the precursors of the above mentioned coagulation factors. substances must be used for two or three months before the pro- Vitamin K1 (0.5-2%) has been used topically to treat actinic pur- cedure to allow some reduction in pigmentation. The post- pura and traumatic purpura resulting from surgeries, and has operative use of whitening substances and sunscreen is essential. been proven to help reduce the amount of extravascular blood Results have been definitive over three years of observation, and ecchymosis. As a result of its antihemorrhagic action, its use without the long-term need to use whitening substances.38 was also tested in the reduction of dark eye circles, however it was scientifically confirmed to cause allergic reactions, increased TREATMENTS WITH FILLERS sensitivity and contact dermatitis at the site of application. It was Another treatment recommended for dark eye circles is subsequently forbidden by ANVISA (Brazilian General Agency filling the nasojugal fold with hyaluronic acid. This substance is of Cosmetics and Sanitary Surveillance), which prohibited the an essential component of the cellular matrix found in all tis- use of vitamin K in cosmetics.34,35 sues; it can retain water, to provide hydration and turgor to the

Surg Cosmet Dermatol 2011;3(3):233-9. 238 Souza DM, Ludtke C, Souza ERM, Scandura KMP, Weber MB

Retro-injection Anterograde in bolus with cannula injection

Figure 5 - Palpebral filling application techniques: A) in bolus, B) retro-injection with cannula and C) Anteroinjection with cannula skin. It is a polysaccharide with a gelatinous consistency, formed 3. Anterograde injection technique (more common in by several interlinked units of disaccharide containing glucuron- Europe): the needle is introduced until it reaches the suprape- ic acid and N-acetyl glycosaminoglycan. It can be extracted riosteal plane, injecting the product at the same time.40,42,45 It is from tissues or biosynthesized by bacteria through fermenta- believed that, since it is viscouselastic, as the product is injected tion.12 it displaces important structures, avoiding intravascular injec- When tractioning the malar region of some patients, a tion.46,47 It is important to apply a gentle massage after the pro- depression below the lower eyelid, medially towards the lachry- cedure. mal duct, can be noticed. That is the area indicated for injecting Goldberg and others described a technique in which sev- hyaluronic acid. Better results are obtained in young patients, eral hyaluronic acid retro-injections are made in a fan-like shape who have less skin and adipose tissue in that area. Based on in the infraorbicular plane, slightly above the periosteum experience and obtained results, it is suggested that the area is (around 20-50 per side).41 Kane39 prefers the application of whitened with pulsed light sessions and the use of topical depig- crossed retro-injections in two planes (deep and infraorbicular menters at home in monthly intervals before the filling proce- dermis, in a sandwich-like manner). Those two techniques have dure. There are several application techniques. The main three a greater likelihood of side effects, such as popular or string are: in bolus; retro-injection with cannula and anterograde injec- hypercorrections, ecchymoses, local hyper or hypopigmenta- tion39 - 45 (Figure 5). tion, ischemia due to intravascular injection, etc.39-45 1. In bolus technique (deep puncture): the area of applica- Autologous fat transplants can also be a good alternative tion is marked in advance with small circles. The needle is then for dark eye circles; the increase in the subcutaneous fat vascu- introduced at a 90° angle. When the deep supraperiosteal plane larization and skin transparency in the periorbital region can be is reached, the needle must be retracted by 1 mm in order to involved in its physiopathogeny.46 A study by Pinski and col- avoid intravascular injection. Next, the product is injected in leagues (1992) 47 demonstrates good results for this procedure, bolus in the site. The procedure is repeated in all marked circles. which seems to be safe, however there is a controversy regard- In order to avoid compromising the ocular lubrication, fillings ing the duration of the results.48,49 are not carried out close to the lachrymal duct. Massage is recommended at the end of the procedure, in order to allow ade- CONCLUSION quate modelling.39,44 Although dark eye circles are a constant complaint in der- 2. Retro-injection with cannula technique: the filling matology practices, they do not yet have a clearly defined etiol- region is marked with the shape of an ellipse and with a circle ogy or therapeutic method. Further studies on its etiology and at the site of the anesthetic button. Next, an incision is made epidemiology should be carried out, so that treatment alterna- with a 27G needle , through which the 25x0.8 cannula (con- tives can be developed for patients. ● nected to the syringe containing the filling material) is introduced. A slight traction is applied in order for the supraperiosteal plane to be reached. The syringe is brought close to the entry orifice in order to inject the filler. If necessary, the procedure is repeated. The cannula is removed and the area is massaged.39

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